Androgens are steroid hormones that play a critical role in brain development and sexual maturation by acting upon both androgen receptors (AR) and estrogen receptors (ERα/β) after aromatization. The ...contribution of estrogens from aromatized androgens in brain development and the central regulation of metabolism, reproduction, and behavior is well defined, but the role of androgens acting on AR has been unappreciated. Here, we map the sex specific expression of Ar in the adult and developing mouse brain. Postnatal days (PND) 12 and 21 were used to target a critical window of prepubertal development. Consistent with previous literature in adults, sex‐specific differences in Ar expression were most profound in the bed nucleus of the stria terminalis (BST), medial amygdala (MEA) and medial preoptic area (MPO). Ar expression was also high in these areas at PND 12 and 21 in both sexes. In addition, we describe extra‐hypothalamic and extra‐limbic areas that show moderate, consistent and similar Ar expression in both sexes at both prepubertal time points. Briefly, Ar expression was observed in olfactory areas of the cerebral cortex, the hippocampus, several thalamic nuclei, and cranial nerve nuclei involved in autonomic sensory and motor function. To further characterize forebrain populations of Ar expressing neurons and determine whether they also coexpress estrogen receptors, we examined expression of Ar, Esr1 and Esr2 in prepubertal mice in selected nuclei. We found populations of neurons in the BST, MEA and MPO that coexpress Ar, but not Esr1 or Esr2, whereas others express a combination of the three receptors. Our findings indicate that various brain areas express Ar during prepubertal development and may play an important role in female neuronal development and physiology.
The neuroanatomical distribution of androgen receptor (Ar) mRNA in male and female mice is described and characterized at two prepubertal time points that frame an active period of brain development. We expand upon previous literature to map Ar distribution in cerebral cortex, thalamus, hypothalamus, and brainstem. Additionally, we identified forebrain sites that coexpress Ar with Esr1 and/or Esr2 during development.
Abstract
Disorders of androgen imbalance, such as hyperandrogenism in females or hypoandrogenism in males, increase risk of visceral adiposity, type 2 diabetes, and infertility. Androgens act upon ...androgen receptors (AR) which are expressed in many tissues. In the brain, AR are abundant in hypothalamic nuclei involved in regulation of reproduction and energy homeostasis, yet the role of androgens acting via AR in specific neuronal populations has not been fully elucidated. Leptin receptor (LepRb)–expressing neurons coexpress AR predominantly in hypothalamic arcuate and ventral premammillary nuclei (ARH and PMv, respectively), with low colocalization in other LepRb neuronal populations, and very low colocalization in the pituitary gland and gonads. Deletion of AR from LepRb-expressing cells (LepRbΔAR) has no effect on body weight, energy expenditure, and glucose homeostasis in male and female mice. However, LepRbΔAR female mice show increased body length later in life, whereas male LepRbΔAR mice show an increase in spontaneous ambulatory activity. LepRbΔAR mice display typical pubertal timing, estrous cycles, and fertility, but increased testosterone levels in males. Removal of sex steroid negative feedback action induced an exaggerated rise in luteinizing hormone in LepRbΔAR males and follicle-stimulating hormone in LepRbΔAR females. Our findings show that AR can directly affect a subset of ARH and PMv neurons in a sex-specific manner and demonstrate specific androgenic actions in the neuroendocrine hypothalamus.
This cross-sectional study quantified differences in (a) social determinants of health (SDOH) and perceived changes in SDOH during the 2019 novel coronavirus (COVID-19) pandemic and (b) COVID-19 ...psychosocial impacts across four groups: (a) non-Hispanic White (NHW) parents of children with asthma, (b) Black, Indigenous, or other People of Color (BIPOC) parents of healthy children, (c) BIPOC parents of children with asthma, and (d) NHW parents of healthy children (referent). The NIMHD Framework was used to identify SDOHs that may change for families during COVID-19.
Parents were recruited via Prolific (N = 321) and completed questions about COVID-19 family impacts on employment, income, access to food and healthcare, and psychosocial functioning, including discrimination. It was hypothesized that NHW families of children with asthma and BIPOC families would endorse greater negative outcomes relative to NHW parents of healthy children.
BIPOC families experienced greater food insecurity and discrimination relative to NHW parents of healthy children. When compared with the NHW healthy group, COVID-19 resulted in greater parent-reported resource losses for both BIPOC groups and greater reductions in healthcare access for both asthma groups. Children with asthma and BIPOC children had greater distress surrounding COVID-19. BIPOC and NHW parents of children with asthma reported greater worries about resource losses due to COVID-19.
The pandemic is widening inequities for BIPOC families, especially for families of children with asthma. These results highlight the need for interventions that address the needs of underserved communities, providing the infrastructure, policies, and supports needed to reduce health inequities during and after COVID-19.
Abstract
Androgens are steroid hormones crucial for sexual differentiation of the brain and reproductive function. In excess, however, androgens may decrease fertility as observed in polycystic ovary ...syndrome, a common endocrine disorder characterized by oligo/anovulation and/or polycystic ovaries. Hyperandrogenism may also disrupt energy homeostasis, inducing higher central adiposity, insulin resistance, and glucose intolerance, which may exacerbate reproductive dysfunction. Androgens bind to androgen receptors (ARs), which are expressed in many reproductive and metabolic tissues, including brain sites that regulate the hypothalamo-pituitary-gonadal axis and energy homeostasis. The neuronal populations affected by androgen excess, however, have not been defined. We and others have shown that, in mice, AR is highly expressed in leptin receptor (LepRb) neurons, particularly in the arcuate (ARH) and the ventral premammillary nuclei (PMv). Here, we assessed if LepRb neurons, which are critical in the central regulation of energy homeostasis and exert permissive actions on puberty and fertility, have a role in the pathogenesis of female hyperandrogenism. Prenatally androgenized (PNA) mice lacking AR in LepRb cells (LepRbΔAR) show no changes in body mass, body composition, glucose homeostasis, or sexual maturation. They do show, however, a remarkable improvement of estrous cycles combined with normalization of ovary morphology compared to PNA controls. Our findings indicate that the prenatal androgenization effects on adult reproductive physiology (ie, anestrus and anovulation) are mediated by a subpopulation of LepRb neurons directly sensitive to androgens. They also suggest that the effects of hyperandrogenism on sexual maturation and reproductive function in adult females are controlled by distinct neural circuits.
Gonadal steroids modulate growth hormone (GH) secretion and the pubertal growth spurt via undefined central pathways. GH-releasing hormone (GHRH) neurons express estrogen receptor α (ERα) and ...androgen receptor (AR), suggesting changing levels of gonadal steroids during puberty directly modulate the somatotropic axis. We generated mice with deletion of ERα in GHRH cells (GHRH
), which displayed reduced body length in both sexes. Timing of puberty onset was similar in both groups, but puberty completion was delayed in GHRH
females. Lack of AR in GHRH cells (GHRH
mice) induced no changes in body length, but puberty completion was also delayed in females. Using a mouse model with two reporter genes, we observed that, while GHRH
neurons minimally colocalize with Kiss1
in prepubertal mice, ∼30% of GHRH neurons coexpressed both reporter genes in adult females, but not in males. Developmental analysis of
and
expression suggested that a subpopulation of ERα neurons in the arcuate nucleus of female mice undergoes a shift in phenotype, from GHRH to Kiss1, during pubertal transition. Our findings demonstrate that direct actions of gonadal steroids in GHRH neurons modulate growth and puberty and indicate that GHRH/Kiss1 dual-phenotype neurons play a sex-specific role in the crosstalk between the somatotropic and gonadotropic axes during pubertal transition.
Late maturing adolescents usually show delayed growth and bone age. At puberty, gonadal steroids have stimulatory effects on the activation of growth and reproductive axes, but the existence of gonadal steroid-sensitive neuronal crosstalk remains undefined. Moreover, the neural basis for the sex differences observed in the clinical arena is unknown. Lack of ERα in GHRH neurons disrupts growth in both sexes and causes pubertal delay in females. Deletion of androgen receptor in GHRH neurons only delayed female puberty. In adult females, not males, a subset of GHRH neurons shift phenotype to start producing Kiss1. Thus, direct estrogen action in GHRH/Kiss1 dual-phenotype neurons modulates growth and puberty and may orchestrate the sex differences in endocrine function observed during pubertal transition.
There is a paucity of data on nicotine and cannabis use among young adults (YAs) with asthma. This study aimed to do the following among YAs with asthma: (1) describe YAs' active and passive exposure ...to nicotine and cannabis; (2) identify latent classes of active use of nicotine and cannabis; and (3) explore predictors of class membership (i.e., demographics, parental and friend use of nicotine and cannabis, and hours of environmental exposure to tobacco smoke, e-cigarette vapor, and marijuana smoke). YAs with asthma (N = 178) self-reported on nicotine and cannabis exposure and the included covariates. Latent class analysis was used to identify latent classes of lifetime nicotine and cannabis use. High rates of nicotine and cannabis use among YAs with asthma were found: 37% reporting a lifetime history of using both nicotine and cannabis. Regarding past year use, 25% had smoked cigarettes, 40% had used e-cigarettes, and 35% had used cannabis. Five classes of lifetime use were identified. The largest class was a non-user class (53%); the other four classes indicate concerning patterns of nicotine and cannabis use. The most consistent predictor of being in a class characterized by more nicotine and cannabis exposure (versus being in the non-user class) was past week exposure to cannabis smoke. This is the first study to identify classes of lifetime nicotine and cannabis use, and examine predictors of class membership, among YAs with asthma. There is a critical need to address environmental and active tobacco and marijuana exposure among YAs with asthma.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Objective: American Indian peoples (AIs) have high smoking rates and cardiovascular risk factor burden. The present study aimed to (a) investigate latent smoking classes across adolescence and ...adulthood, (b) investigate adolescent predictors of smoking classes, and (c) assess how smoking class is related to adult cardiovascular risk in a sample of AIs. Method: A sample of AIs (N = 338) from the National Adolescent to Adult Health Study self-reported on smoking across four assessment waves (W1: 7th-12th grade; W2: 8th-12th grade; W3: ages 18-26; W4: ages 24-32). The socioecological framework for addressing tobacco-related disparities was used to identify potential adolescent (W1) risk and resource factors. C-reactive protein, blood pressure, and lipids were collected at W4. Growth mixture modeling and regressions were used. Results: Six smoking classes were identified: light smoking (36%), nonsmoking (23%), escalating, adult daily smoking (13%), chronic heavy smoking (12%), escalating, young adult daily smoking (9%), and reducing smoking (7%). Risk factors for being in the chronic heavy smoking class included peer smoking and older age at W1. Compared with the chronic heavy smoking class, AIs in the reducing smoking class lived in in more impoverished neighborhoods during adolescence. Relative to several classes with less smoking, being in the chronic heavy smoking class was associated with higher C-reactive protein and less favorable lipid levels. W1 social support was a resource factor for adult diastolic blood pressure and some lipids. Conclusions: Socioecologically informed tobacco interventions have the potential to reduce smoking and cardiovascular risk among AIs, and bolstering social support may be important.
Objective: To better understand mechanisms influencing health in African Americans (AAs), the aims of this study were (a) to identify longitudinal cigarette smoking classes among AAs across ...adolescence and into young adulthood; (b) to identify risk factors for smoking and how cardiometabolic health in adulthood differs by smoking class; and (c) to investigate whether smoking mediates the relation between adolescent risk factors and adult cardiometabolic health. Method: This study used 4 waves of nationally representative data, restricted to an AA subsample (N = 2,009). Participants self-reported on multilevel risk factors in adolescence and smoking across adolescence and young adulthood; cardiometabolic risk was assessed in adulthood. Growth mixture modeling and structural equation modeling were conducted. Results: Five classes emerged: nonsmoker; early onset, heavier smoking; later onset; early onset, light smoking; and maturing out or declining smoking. Predictors of class membership included living with individuals who smoke, having friends who smoke, and limited access to medical care. The early onset, light smoking class had the greatest cardiometabolic risk. Smoking class mediated the relation between living with people who smoke in adolescence and adult cardiometabolic risk. Conclusions: Nuanced smoking patterns among AAs were identified, and 23% fell into classes characterized by an early onset and persistent smoking trajectory. The early onset, light smoking class had the greatest cardiometabolic risk in adulthood. The results suggest unique protective factors may be present for youth who remain nonsmokers even when their family smokes. Results have implications for health promotion and tobacco prevention efforts among AA families.
Nontuberculous mycobacteria (NTM), predominately Mycobacterium avium complex (MAC), cause chronic pulmonary disease. Improvements in symptoms and health-related quality of life (HRQoL) are important ...treatment outcomes, but no validated patient-reported outcome (PRO) measure exists.
What are the validity and responsiveness of the Quality of Life-Bronchiectasis (QOL-B) questionnaire respiratory symptoms scale and key HRQoL measures during the first 6 months of MAC pulmonary disease (MAC-PD) treatment?
Comparison of Two- vs Three-antibiotic Therapy for Pulmonary Mycobacterium Avium Complex Disease (MAC2v3) is an ongoing randomized, multisite pragmatic clinical trial. Patients with MAC-PD were randomized to azithromycin-based two-drug or three-drug therapy; treatment groups were combined for this analysis. PROs were measured at baseline, 3 months, and 6 months. The QOL-B respiratory symptoms, vitality, physical functioning, health perceptions, and NTM symptom domain scores (on a scale of 0-100, with 100 being best) were analyzed separately. We performed psychometric and descriptive analyses in the population enrolled as of the time of analysis and calculated the minimal important difference (MID) using distribution-based methods. Finally, we evaluated responsiveness using paired t tests and latent growth curve analysis in the subset with longitudinal surveys completed by the time of analysis.
The baseline population included 228 patients, of whom 144 had completed longitudinal surveys. Patients predominately were female (82%) and had bronchiectasis (88%); 50% were 70 years of age or older. The respiratory symptoms domain showed good psychometric properties (no floor or ceiling effects; Cronbach’s α, 0.85) and an MID of 6.4 to 6.9. Vitality and health perceptions domain scores performed similarly. Respiratory symptoms domain scores improved by 7.8 points (P < .0001) and 7.5 points (P < .0001), and the physical functioning domain score improved by 4.6 points (P < .003) and 4.2 points (P = .01) at 3 and 6 months, respectively. Latent growth curve analysis confirmed a nonlinear, statistically significant improvement in respiratory symptoms and physical functioning domain scores by 3 months.
The QOL-B respiratory symptoms and physical functioning scales exhibited good psychometric properties in patients with MAC-PD. Respiratory symptoms scores improved beyond the MID by 3 months after treatment initiation.
ClinicalTrials.gov; No.: NCT03672630; URL: www.clinicaltrials.gov
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